ACE-083 Phase 2 trial results presented at AAN conference

Preliminary results from the ongoing phase 2 clinical trial of ACE-083 in FSHD patients were presented today at the American Academy of Neurology 70th Annual Meeting in Los Angeles, California.The oral presentation by Jeffery Statland, MD, of the University of Kansas Medical Center, included preliminary findings from cohorts 1 and 2 in the open-label, dose escalation Part 1 of the trial.

The presentation was selected for the “Best of” Session in clinical trial updates in neuromuscular disorders. This designation was given to only 24 abstracts out of some 3,000!

Developed by Cambridge-based biotech Acceleron Pharma, ACE-083 consists of a modified form of human follistatin that binds GDF8 (myostatin) plus other molecules that suppress skeletal muscle growth. The drug, which is injected directly into affected muscles, is intended to help FSHD muscles grow by removing a natural “brake system” that keeps normal muscles from excessive growth. In FSHD, muscles are struggling to overcome the disease process, and the idea is that by taking off the “brakes”, they would be able to regenerate better. (See related story.)

The trial results appear to bear out this prediction, with increases in muscle volume of 15-20 percent reported at the higher dose (200 mg) and a decline of the fat-to-muscle ratio especially in the tibialis anterior (shin muscle). As muscle degenerates, it is replaced by fat, so a lowering of the fat-to-muscle ratio indicates that the proportion of muscle relative to fat had increased after treatment.

ACE-083 is currently being evaluated in two Phase 2 trials: one in FSHD and one in Charcot-Marie-Tooth (CMT) disease. The final Part 1 results from both Phase 2 trials are expected in the second of half of 2018.

The randomized, double-blind, placebo controlled Part 2 of the FSHD study has been initiated, with results expected in the second half of 2019. Part 2 of the CMT trial is expected to be initiated by the end of 2018.

Reference: Preliminary Results from a Phase 2 Study to Evaluate ACE-083, a Local Muscle Therapeutic, in Patients with Facioscapulohumeral Muscular Dystrophy. 2018 American Academy of Neurology . April 21-27, 2018.

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Thanks for the news. But increase in muscles volume doesn’t mean increased strength, does it ?
“Preliminarily, correlations were observed for baseline contractile muscle with strength by manual muscle testing” is a bit short…
I hope in the second phase they plan more interesting measures as 6′ walking distance or else.
Sylvie, from AFM FSH group in France

It is good to learn that the second phase will measure changes in strength, which will determine if it will really benefit FSHD people. In the second phase, will you be testing increased dosages? I think the initial phases focused on the shin muscle and the ankle muscle. Will subsequent phases look at alternate muscle areas. In particular, is there any possibility of addressing core muscles? Everyone is encouraged that this development and testing is happening, particularly since the initial phase did produce some positive results.

The ACE-083 trial requires multiple visits to the study site, so it may not be practical for your son. Please bear in mind that a clinical trial is an experiment. ACE-083 has not yet been proven to be effective in FSHD. If possible, you might want to have your son seen at an FSHD clinic in Europe. France, Italy, the Netherlands, and the UK have leading FSHD centers. Please also join the FSH Society. This way, you will receive news updates from the Society and be contacted by the research center when they need to recruit volunteers for studies. Treatments are coming over the next few years, and it’s important to seek good care to manage your son’s FSHD symptoms, maintain an appropriate exercise regimen and have a healthy diet.

As FSHD affects many muscle groups and this is a drug that is intended to be administered via injection what’s the plan when/ if approved ? If it helps I don’t mind receiving any number of injections but if it will be restricted to those muscle groups included in the trial it will be disappointing.
Also as it has now received fast track status from the FDA is it possible that it may receive approval after phase II is completed ?

We suppose that the current Acceleron trial is studying a limited number of muscles (bicep and tibialis anterior) in order to be able to reduce the number of variables in the trial. They have established protocols for measuring the volume and strength of these particular muscles, which provides better standardized, “cleaner” data for the clinical trial. If the trial demonstrates efficacy in these muscles, and the FDA approves ACE-083 for FSHD, it would be reasonable to think that doctors will be able to prescribe injections in other skeletal muscles that are affected in an individual patient.